Borane-tetrahydrofuran complex (sometimes referred to as THFB) is a valuable reagent for the reduction of functional groups and for hydroboration reactions with carbon-carbon double and triple bonds. Functional groups reduced by borane-tetrahydrofuran complex include aldehyde, ketone, acyl chloride, lactone, epoxide, ester, amide, oxime, imine, and nitrile. Borane-tetrahydrofuran complex is a very selective and efficient reducing agent. Typically a reduction is quenched with excess methanol to deactivate any remaining borane-tetrahydrofuran complex and distilled to remove the boron from the desired products as the methylborate/methanol azeotrope.
Unfortunately, borane-tetrahydrofuran complex has been commercially available only as 1 molar solutions for a number of years. In the interest of conservation of resources and efficient use of reactor vessels, however, one would like to conduct reactions at the highest concentration possible for a particular reaction. In that regard, the low concentration of the borane-tetrahydrofuran complex leads to low reactor loading and inefficient use of equipment.
Other more concentrated borane reagents are available but each has inherent disadvantages. For example, sulfide boranes are highly concentrated but suffer from noxious odors. Concentrated amine boranes are also available, but are often not sufficiently reactive to reduce the desired functional groups. In addition, such complexing agents (amine or sulfide) are often difficult to remove from the desired product. Diborane typically requires cryogenic storage conditions (for example, less than -100.degree. C.) to maintain high purity.
In U.S. Pat. No. 3,634,277, Brown demonstrated that borane-tetrahydrofuran complex could be somewhat stabilized from ring-opening ether cleavage of the tetrahydrofuran (THF) by the addition of borohydride or use of excess borohydride in the synthesis. The THFB solutions of U.S. Pat. No. 3,634,277 were made by an in situ process of generating the borane from excess sodium or potassium borohydride and boron trifluoride. Although a range is not given for the concentrations of THFB stabilized by borohydride in U.S. Pat. No. 3,634,277, all the examples thereof described concentrations of 1.5 to 2.0 M THFB. Shelf-life/stability experiments were conducted at ambient temperature for eight weeks. Significant decomposition of the borane-tetrahydrofuran complex was observed even over that short time span.
Notwithstanding the disclosure in U.S. Pat. No. 3,634,277 of the synthesis of relatively highly concentrated borane-tetrahydrofuran complex, Brown and others in the literature have indicated that solutions of borane-tetrahydrofuran complex of greater than 1 M are unavailable as a result of the instability of such solutions. See, for example, H. C. Brown, P. Heim, N. M. Yoon JACS, 92, 1637-1646 (1970); C. F. Lane Chem. Rev., 76, 773-799 (1976); H. C. Brown, M. C. Desai, P. K. Jadhav JOC, 47, 5065-5069 (1982); M. Follet Chem. And Industry., 123-128; and K. Smith, Chem. and Industry 1987, 603-611 (1986).
In addition to decomposing during storage, borane-tetrahydrofuran complexes also thermally decompose in the course of reaction thereof at elevated temperatures. To achieve complete reduction of a functional group, excess borane-tetrahydrofuran complex is typically required. Use of excess borane reagent adds to the cost of the desired reduction and can lead to impurity formation. It is desirable to use only the stoichiometric amount of reducing agent both from the financial and environmental standpoints.
It is, therefore, very desirable to develop compositions and methods to achieve more efficient use of borane-tetrahydrofuran complex.